Lea C. Dacy
Center for Multiple Sclerosis and Demyelinating Diseases (CMSDD)
Mayo Clinic, Rochester, Minnesota, United States
Professor of Immunology and Neurology
Mayo Clinic, Rochester, Minnesota, United States (Fall 2014)
|Enhanced portrait of cellist by www.AB-Photography.us. Used with permission of subject and photographer.|
Although promoted as a “comeback,” it was almost her last public performance. In February 1973, the late Jacqueline du Pré performed the Elgar Cello Concerto in London with the New Philharmonia Orchestra conducted by Zubin Mehta. The concerto had been closely associated with du Pré since her landmark recording in 1965 (at age 20) for EMI with the London Symphony Orchestra conducted by Sir John Barbirolli.1,2 In the audience, her sister noticed du Pré’s uncharacteristically sluggish beginning tempo; for several measures Mehta struggled to bring soloist and orchestra together.3 However, few audience members perceived any difficulties, and du Pré received her usual standing ovation.
In her final concerts, du Pré compensated for early symptoms of multiple sclerosis (MS), using sight rather than her diminished tactile sense to position her fingers and judge how much weight to apply to the bow. Jacqueline du Pré’s stellar performance career lasted only ten years. For classical music devotees, the official confirmation of her diagnosis highlighted the heartbreak of MS. Called the disabler of young adults, MS symptoms typically appear between ages twenty and forty. This tendency to target individuals just embarking on careers, relationships, and parenthood is one of the cruelest aspects of the disease. Today, however, more treatment options are available to combat symptoms as they appear, and experimental treatments currently in clinical trials may be able to reverse neurological damage.
The cello, violin, viola, and string bass have no frets on the fingerboard. A teacher of young musicians occasionally marks first-position stops in pencil to instill confidence but warns the beginner not to depend on visual cues; ideally, the pupil’s aural and tactile senses will work together to produce a quality tone when the pencil marking wears off. Likewise, the bow in the right hand sets a mood through pressure and articulation. A tall, well-built child, du Pré produced a dramatic, full-bodied sound from her earliest lessons. English cellist William Pleeth and subsequent teachers helped her to modulate passages requiring subtler tones. (Her intermittent, unpredictable loss of these abilities while still performing certainly induced a stress well beyond the typical gait and incontinence anxieties experienced by MS patients venturing out in public.) Spinal-cord lesions probably caused loss of feeling in her hands. For the cellist, loss of “position sense,” i.e., knowing where the fingers are precisely in space, would be devastating. Longitudinal tracts in the back of the spinal cord (the dorsal columns) mediate position sense. The central nervous system (CNS) permits precise (~1 mm) perception of where the fingers are in space. Clearly for du Pré, or even novice cellists, deficient spatial discernment would severely hamper musicianship.
LP sets offered du Pré’s pre-MS biography in words and pictures as well as music. An original 1965 recording of the Elgar depicts a grim-faced, chunky girl leaning into her cello. Liner notes describe years of lessons and practice (at, the reader infers, the expense of other activities). The Elgar was an odd choice for a young musician; Edward Elgar composed it near the end of his life while despondent over World War I, his wife’s death, and his own physical infirmities. However, du Pré gave a remarkably sophisticated performance. Side B offered crowd-pleasers such as Saint-Saens “The Swan” and Bruch’s “Kol Nidrei” recorded in her teens. Like a fairy-tale ending, the double LP album entitled “Close Up” featured a slimmer, more attractive du Pré with pianist/husband Daniel Barenboim on the Brahms Sonata No. 2 and Barenboim conducting while du Pré soloed on the Boccherini concerto. Liner notes described their meeting, whirlwind courtship, Jerusalem-based wedding following the Six-Day War and subsequent careers. However, even as the couple rode a wave of public adoration usually reserved for rock stars, du Pré experienced fatigue, a common early symptom of MS, and finger paresthesia (tingling). In November 1973, just months after the Elgar performance, news of du Pré’s MS-induced retirement shocked music lovers all over the world.4
Given concerns about falls, unsteadiness, and incontinence, newly diagnosed MS patients often withdraw from social contact.5 Early in the course of relapsing-remitting MS, episodes of worsening symptoms (exacerbation) precede almost complete resolution (remission). Exacerbations depend on which part of the central nervous system (CNS) develops inflammatory lesions (“plaques”) followed by loss of myelin (demyelination). The CNS includes brain and spinal-cord nerves. (Nerves leaving the brain and spinal cord comprise the peripheral nervous system.) MS affects only the CNS, which controls vision, speech, gait, bladder, and cognition, any of which manifest symptoms (what the patient feels) and signs (what the neurologist finds on clinical examination).
Following her announced diagnosis and retirement, du Pré raised funds for MS research. With Barenboim, she established the Jacqueline du Pré Research Fund under the auspices of the Multiple Sclerosis International Federation (MSIF).6 The du Pré fellowships fund year-long travel grants for early-career MS researchers. Seed money came from a series of fund-raising concerts staged by Barenboim, Mehta, and other renowned classical musicians.7,8 After receiving the Order of the British Empire in 1976, du Pré agreed to a series of BBC TV interviews and also addressed a standing-room-only crowd of MS patients and relatives to launch CRACK, a young people’s support group within the British MS Society. Determinedly upbeat when discussing her disease publicly, she tried to convey that teaching cello and other activities, such as studying poetry, compensated for being unable to perform.9-11
However, du Pré had marginal interest in becoming a celebrity spokesperson for MS and admitted privately that even teaching provided her with little satisfaction.12,13She lived to play the cello. As she described it: “I love to play the cello . . . when I’m playing, I’m happy. It’s that feeling of happiness when one makes music and the joy of feeling the music as well as playing it.”14 Certainly, this “pay-off” is essential for a youngster pursuing the lonely life of a prodigy, a life du Pré had prepared for since age 4. No special academies for gifted children then existed in the United Kingdom. Du Pré’s parents, secondary school teachers and Pleeth arranged her schoolwork to meet basic educational requirements while allowing maximal time for practice (and virtually no social life).15-16 Du Pré attributed her lifelong social awkwardness and cultural illiteracy to these decisions made on her behalf. Indeed, biographer Carol Easton, who met du Pré in the last years of her life, noted that “she claimed never to have heard of Gone with the Wind, or Paul Newman, or Charlie Parker.”17 While even other musicians were tempted to blame her parents and Pleeth for not providing more balance, the single-minded dedication to the cello was Jacqueline’s choice. Calling the cello her best friend, she was ill-prepared for life without it when MS finally took control of her body. “It was my gorgeous secret – an inanimate object, but I would tell it all my sadness and my problems. It gave me everything I needed and wanted.”18 She found a somewhat bittersweet comfort in listening to her own re-released recordings on EMI of Kol Nidrei, Faure’s Elegie, and, of course, the Elgar concerto because she knew she would never record again.19
The onset of du Pré’s disease is elusive. Often, after a definitive diagnosis, the patient or family tries to link it to earlier illnesses or puzzling events. During her teens, du Pré had episodes of blurred vision, often indicative of MS. However, it is unclear whether her frequent falls were indicative of MS or just the clumsiness of a rather sedentary young person. An episode of what her family described as “glandular fever” led to her first meeting (by telephone) with Barenboim, who was suffering from a similar complaint.20 Later, an inexplicably long episode of laryngitis and glandular enlargement unrelated to a cold (possibly Epstein-Barr virus infection) prompted du Pré to seek medical attention while touring in Australia with Barenboim.21 A virus such as this may have triggered her disease.22
Du Pré’s disease seemingly meets the criteria for relapsing remitting MS with secondary progression. (For a current classification of MS phases and categories, see Kantarci et al. http://www.ncbi.nlm.nih.gov/pubmed/24173041.)23 When du Pré’s initial symptoms appeared, few effective symptomatic treatments existed. While steroids shortened the duration of disability following an acute attack, this treatment did not affect the ultimate outcome. Her siblings reported she experienced temporary symptomatic relief that ended when steroids were stopped.24
MS has traditionally been attributed to an abnormal immune response. The alternative hypothesis is that it is triggered by a virus. Our bodies secrete interferon during viral infections to prevent the viral insult from spreading to other healthy cells. Observing dramatic effects in animal models of MS, scientists discovered almost simultaneously three different forms of interferon that prevent new attacks and new brain-lesion formation. Additionally, glatiramer acetate (Copaxone), peptides containing 4 essential amino acids, prevents relapses and decreases MRI burden.25 Other more aggressive immunosuppressants, effective in clinical trials, are now approved second-tier treatments in advanced forms of the disease but may have serious side effects.25
Patients experiencing acute fulminant attacks resulting in paraplegia or quadriplegia often benefit from plasma exchange given within three months of attack onset; approximately 40% recover almost completely, simulating a “Lazarus” effect.26 Exchanging the entire blood volume every other day for seven treatments eliminates toxins that attack the myelin nerve-protecting sheath. To enhance functional recovery in patients incapacitated from acute attacks or chronic progression, investigators are seeking to develop approaches to regenerate myelin or even neurons.27 Antibodies invented at the Mayo Clinic, now in Phase I trials, stimulate myelin growth directly or block remyelination-inhibiting substances (anti-NoGo therapy).28 It is poignant to speculate whether such treatments might have saved du Pré’s life and career. Fortunately, her extraordinary recordings remain for us to cherish, and the incredible advancements in the treatment of MS spring directly from basic-science research funded twenty years previously through mechanisms like the du Pré Fellowships.
- Wilson E. Jacqueline du Pré: Her Life, Her Music, Her Legend. New York: Arcade Publishing; 1988, 170-75.
- Vittes L. How Jacqueline du Pré Sparked a Cello Explosion. Strings. 2012. http://www.allthingsstrings.com/News/Interviews-Profiles/How-Jacqueline-du-Pre-Sparked-a-Cello-Explosion
- du Pré H, du Pré P. A Genius in the Family: An Intimate Memoir of Jacqueline du Pré. London: Vantage U.K. Random House; 1998, pages 284-86.
- Wilson E. Jacqueline du Pré, 404.
- Halper J. The psychosocial effect of multiple sclerosis: the impact of relapses. J Neurol Sci. May 15 2007;256 Suppl 1:S34-38.
- Du Pré Grants. http://www.msif.org/about-us/international-ms-research/research-awards-grants-and-fellowship/du-pr%C3%A9-grants/
- Wilson E. Jacqueline du Pré, 416.
- The Jacqueline du Pré Research Fund for Multiple Sclerosis in Jacqueline du Pré: Impressions, ed. William Wordsworth (New York: The Vanguard Press, 1983), 143-44.
- du Pré and du Pré. A Genius in the Family, 316-17.
- du Pré J, Wordsworth W. ‘I Was Lucky, You See’ (Compiled from Conversations with the Editor and BBC Interviews). in Jacqueline du Pré: Impressions, ed. William Wordsworth (New York: The Vanguard Press, 1983), 129-34.
- Wilson E. Jacqueline du Pré, 408.
- Easton C. Jacqueline du Pré: A Biography. Boston, MA: Da Capo Press; 1989, 202.
- Wilson E. Jacqueline du Pré,416, 424.
- Easton C. Jacqueline du Pré, 121.
- Wilson E. Jacqueline du Pré, 25-33, 52.
- Easton C. Jacqueline du Pré, 11-12.
- Easton C. Jacqueline du Pré, 17.
- Easton C. Jacqueline du Pré, 47.
- Wilson E. Jacqueline du Pré,424-26, 438.
- du Pré and du Pré. A Genius in the Family, 187-88.
- Wilson E. Jacqueline du Pré, 374-77.
- Rodriguez M, Kantarci OH, Pirko I. What has immunology taught us about multiple sclerosis? in Multiple Sclerosis. New York: Oxford University Press; 2013:98-116.
- Kantarci OH, Pirko I, Rodriguez M. Novel Immunomodulatory Approaches for the Management of Multiple Sclerosis. Clin Pharmacol Ther. Oct 30 2013.
- du Pré and du Pré. A Genius in the Family, 306.
- Rodriguez M, Kantarci OH, Pirko I. Managing Symptoms of Multiple Sclerosis. in Multiple Sclerosis. New York: Oxford University Press; 2013:154-167.
- Rodriguez M, Karnes WE, Bartleson JD, Pineda AA. Plasmapheresis in acute episodes of fulminant CNS inflammatory demyelination. Neurology. Jun 1993;43(6):1100-1104.
- Rodriguez M, Kantarci OH, Pirko I. Future Disease-modifying Treatment Approaches in Multiple Sclerosis. in Multiple Sclerosis. New York: Oxford University Press; 2013:172-175.
- “An Intravenous Infusion Study of rHIgM22 in Patients With Multiple Sclerosis,” last modified January 22, 2014, http://www.clinicaltrials.gov/ct2/show/NCT01803867?term=rHIgM22&rank=1.
LEA C. DACY, AB, is Secretary of the Mayo Clinic Center of Multiple Sclerosis and Demyelinating Diseases, a freelance cellist, and owner of e-Cello!® Music.
MOSES RODRIGUEZ, MD, is Professor of Immunology and Neurology at Mayo Clinic. His laboratory discovered the remyelinating properties of recombinant antibody rHIgM22. A musician and arranger, Dr. Rodriguez plays trombone in several groups and directs Trombones Anonymous. His previous work includes Rodriguez et al., Multiple Sclerosis (Contemporary Neurology Series); New York: Oxford University Press, 2013, which Ms. Dacy edited.
Disclosures: Patents for antibodies that promote remyelination and CNS repair are issued and owned by Mayo Foundation; therefore, Dr. Rodriguez has a potential conflict of interest. Both authors receive royalties from the sale of Multiple Sclerosis.
Highlighted in Frontispiece Fall 2014 – Volume 6, Issue 4